Osteolytic Lesions Research Articles

ASPECTS EPIDEMIOLOGIQUES, DIAGNOSTIQUES ET THERAPEUTIQUES DES ADENOMES CORTICOTROPES AU CENTRE HOSPITALIER NATIONAL UNIVERSITAIRE (CHNU) DE FANN

Introduction: Primary bone cancers account for less than 0.2% of malignancies. There are preferential locations according to the histological type. Objective: to study the epidemiological, diagnostic, therapeutic and evolutionary aspects of primary malignant bone tumors. Patients and method: This was a retrospective study of data from January 1, 2012 to December 31, 2022 on malignant bone tumors at the Gabriel Touré CHU. Results: During our study the hospital frequency was 0.10%. The sex ratio was 1.8 and the average age of patients 37.9. The average time to visit the hospital was six months. Biopsy was the majority 63.9%. The diagnosis has always been confirmed by anatomopathology. Osteosarcomas were common 27.78%. Well-differentiated forms accounted for 58.36%. The multidisciplinary consultation meeting was held in 36.33% of patients and 47.22% of patients received chemotherapy. Excision was the most commonly used surgical procedure 50% of cases. The survival rate was 30.6% at 5 years. Conclusion: Malignant primary bone tumors are relatively rare at Gabriel Toure UHC. Preferred location was the femur. The majority of our patients were seen late with advanced osteolytic lesions. The most common histological type was osteosarcoma. The low rate of amputation and improved survival under treatment are well known. However, survival at 5 years remains reserved.

From Tumor to Bone: Growth Factor Receptors as Key Players in Cancer Metastasis.

This review article explores the intricate correlation between growth factors and bone metastases, which play a crucial role in the development of several types of malignancies, namely breast, prostate, lung, and renal cancers. The focal point of our discussion is on crucial receptors for growth factors, including Epidermal Growth Factor Receptor (EGFR), Transforming Growth Factor-β (TGFβ), Vascular Endothelial Growth Factor Receptor (VEGFR), and Fibroblast Growth Factor Receptor (FGFR). These receptors, which are essential for cellular activities including growth, differentiation, and survival, have important involvement in the spread of cancer and the interactions between tumors and the bone environment. We discuss the underlying mechanisms of bone metastases, with a specific emphasis on the interaction between growth factor receptors and the bone microenvironment. EGFR signaling specifically enhances the process of osteoclast development and the formation of osteolytic lesions, especially in breast and lung malignancies. TGFβ receptors have a role in both osteolytic and osteoblastic metastases by releasing TGFβ, which attracts cancer cells and promotes bone remodeling. This is a crucial element in the spread of prostate cancer to the bones. The functions of FGFR and VEGFR in the processes of bone formation and tumor angiogenesis, respectively, highlight the complex and diverse nature of these interactions. The review emphasizes the possibility of targeted therapeutics targeting these receptors to interrupt the cycle of tumor development and bone degradation. Therapeutic approaches include focusing on the VEGF/VEGFR, EGF/EGFR, FGF/FGFR, and TGFβ/TGFβR pathways. These include a variety of compounds, such as small molecule inhibitors and monoclonal antibodies, which have shown potential to interfere with tumor-induced alterations in bone. The text discusses clinical trials and preclinical models, offering insights into the effectiveness and constraints of various treatments. Ultimately, this study provides a succinct but thorough summary of the present knowledge and treatment strategies focused on growth factor receptors in bone metastases. This highlights the significance of comprehending the signaling of growth factor receptors in the microenvironment where tumors spread to the bones, as well as the possibility of using targeted therapies to enhance the results for cancer patients with bone metastases. The advancement of treating bone metastases hinges on the development of treatments that specifically target the intricate relationships between malignancies and bone.

Cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles inhibits breast cancer-bone metastasis by targeting JAK-STAT signaling pathways

Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.

Estradiol induces bone osteolysis in triple-negative breast cancer via its membrane-associated receptor ERα36.

Triple-negative breast cancer (TNBC) is thought to be an estradiol-independent, hormone therapy-resistant cancer because of lack of estrogen receptor alpha 66 (ERα66). We identified a membrane-bound splice variant, ERα36, in TNBC cells that responds to estrogen (E2) and may contribute to bone osteolysis. We demonstrated that the MDA-MB-231 TNBC cell line, which expresses ERα36 similarly to MCF7 cells, is responsive to E2, forming osteolytic tumors in vivo. MDA-MB-231 cells activate osteoclasts in a paracrine manner. Conditioned media (CM) from MDA-MB-231 cells treated with bovine serum albumin-bound E2 (E2-BSA) increased activation of human osteoclast precursor cells; this was blocked by addition of anti-ERα36 antibody to the MDA-MB-231 cultures. Osteoclast activation and bone resorption genes were elevated in RAW 264.7 murine macrophages following treatment with E2-BSA-stimulated MDA-MB-231 CM. E2 and E2-BSA increased phospholipase C (PLC) and protein kinase C (PKC) activity in MDA-MB-231 cells. To examine the role of ERα36 signaling in bone osteolysis in TNBC, we used our bone-cancer interface mouse model in female athymic homozygous Foxn1nu mice. Mice with MDA-MB-231 tumors and treated with tamoxifen (TAM), E2, or TAM/E2 exhibited increased osteolysis, cortical bone breakdown, pathologic fracture, and tumor volume; the combined E2/TAM group also had reduced bone volume. These results suggest that E2 increased osteolytic lesions in TNBC through a membrane-mediated PLC/PKC pathway involving ERα36, which was enhanced by TAM, demonstrating the role of ERα36 and its membrane-associated signaling pathway in bone tumors. This work suggests that ERα36 may be a potential therapeutic target in patients with TNBC.

A Very Rare Relaps Type in Multiple Myeloma: Leptomenıngeal and Cranial Involvement

Multiple myeloma is a hematological malignancy that develops as a result of clonal proliferation of plasma cells and progresses with remissions and relapses. It is clinically characterized by many symptoms and signs such as osteolytic bone lesions, hypercalcemia, renal dysfunction, hypergammaglobulinemia and anemia. However, involvement of the central nervous system, especially the leptomeningeal/cranial region, is a rare and prognostically important form of relapse of the disease. This case report discusses this rare clinical presentation, diagnostic approach, and treatment strategies of extramedullary involvement of multiple myeloma.

Cutaneous and Osseous Histoplasmosis caused by Histoplasma capsulatum var. duboisii in a Seemingly Immunocompetent Young Senegalese Woman

African histoplasmosis is a rare deep mycosis caused by Histoplasma capsulatum var duboisii. It can affect various organs such as the skin, lymph nodes, and bones. The diagnosis is often delayed due to its similarity to certain diseases such as tuberculosis, cryptococcosis, pyogenic abscesses, and even neoplasia. We report a case of cutaneous and osseous histoplasmosis caused by H. capsulatum var. duboisii in a seemingly immunocompetent 19-year-old senegalese woman who presented with chronic disseminated cutaneous abscesses, some of which had fistulised, and umbilicated papules on the face. The radiograph of the right forearm showed a metaphyso-diaphyseal osteolytic lesion of the ulna. Histology after biopsy of a facial papule confirmed the diagnosis of histoplasmosis caused by H. capsulatum var duboisii. The patient's condition improved with fluconazole treatment.

Osteolytic Lesions in a Sub-Adult Loggerhead Sea Turtle (Caretta caretta): A Case Report.

Osteolytic lesions in loggerhead sea turtles (Caretta caretta) during rehabilitation are attributed to multiple causes, including gas embolism, hypothermia, and osteomyelitis due to bacterial or fungal infection. This study reports the appearance of osteolytic lesions in a sub-adult loggerhead sea turtle with involvement of the right fore and hind flippers, visible swelling of the elbow and knee joints, and accompanied by lameness after 45 days of rehabilitation. Radiographs and computed tomography revealed multiple lytic bone lesions. This was the fourth rehabilitation admission of the turtle after being accidentally captured by trawler ships (bycatch) in 2019, 2020, 2022, and 2023. Potential causes were dysbaric osteonecrosis due to a past decompression sickness event and hypothermia with osteomyelitis from bacterial infection. Blood cultures and antibiotic susceptibility testing led to the isolation of Ewingella americana responsive to enrofloxacin. This study investigates extensive fore and hind flipper involvement in a sub-adult loggerhead turtle, aiming to determine causes and risk factors. The pathogenesis and significance of these lesions is discussed.

Analysis of the effectiveness and efficiency of the Indonesian metastatic bone disease of unknown origin algorithm (INA-MBD): time to diagnosis and cost to diagnosis : Quasi-experimental study

Background Patients with Metastatic Bone Disease (MBD) often presenting with complaints of pain and multiple osteolytic lesions findings. Remarkably, 30% of these cases exhibit an undetected primary lesion. Hence, categorizing them as MBD of unknown origin. The diagnostic processes of patients with MBD of unknown origin typically takes up to four months, rendering it as a catastrophic disease with the second-highest financial burden. Given its urgency, it is necessary to develop a systematic and evidence-based consensus for managing cases of MBD with an unknown origin. Purpose This study aimed to enhance the effectiveness and efficiency of treating patients with MBD of unknown origin through the application of the INA-MBD algorithm. Research method A quasi-experimental study with a pretest and post-test design was conducted with a total of 128 patients who met the inclusion and exclusion criteria. The patients were consecutively enrolled and categorized into two groups: the intervention group with the INA-MBD algorithm and the non-intervention group without the INA-MBD algorithm. The primary outcomes were the cost and time to diagnose MBD of unknown origin. The proposed measuring tool was the INA-MBD algorithm. Furthermore, for the cost-to-diagnosis variable, an extra measurement tool was used, which were summaries of the patient’s medical bill including hospital stays and medical procedures. The analysis of data related to the time-to-diagnosis variable was conducted using the Log Rank regression test, and cost-to-diagnosis variable was carried out using co-variance test.

Isolated calvarial aneurysmal bone cyst in a pediatric patient: illustrative case.

Aneurysmal bone cysts (ABCs) are benign, osteolytic lesions that can occur in long bones, vertebrae, or rarely, the skull. Here the authors present the case of a 15-year-old male with a primary ABC of the left frontoparietal skull along with a review of the literature to provide insight into the nature of this rare disease. An otherwise healthy 15-year-old male presented with a tense, painful lesion of the left frontoparietal scalp. He could not identify any inciting trauma, but first noted the lesion less than 2 weeks prior to presentation with progressive enlargement. Cranial imaging revealed a lytic skull lesion with fluid-fluid levels suggestive of ABC. Curative therapy was provided via wide excision of the lesion and calvarial reconstruction of the resultant skull defect. This was performed without complication, and histopathological evaluation confirmed the diagnosis of primary ABC. ABCs of the skull are rare entities and most often arise in the skull base versus the calvaria. Typically, these lesions are associated with an underlying bone pathology (secondary ABCs) but can be rarely seen as isolated lesions (primary ABCs). Clinical management consists of excision and adjuvant therapy for underlying pathology where appropriate.

Tebentafusp in the treatment of metastatic uveal melanoma - the first patient treated in the Czech Republic.

Uveal melanoma is a rare cancer, in which metastases occur in approximately one half of cases. In metastatic disease, the prognosis is unfavorable and the median of survival does not exceed 6 months. Effective treatment options were very limited up to date. Tebentafusp is a bispecific fusion protein, which as the first drug proved efficacy in uveal melanoma. The patient was referred for suspected uveal melanoma of the left eye. She was treated for Hodgkin's disease in the past. Primarily, the tumor was treated by radiosurgery with radiotherapy of a small lesion of the vertebral body. However, later the patient had to undergo bulbus enucleation with confirmation of a large tumor category pT4b. PET/CT revealed metastases of the bones and the liver; simultaneously, haplotype A*02: 01 was confirmed. The patient underwent radiotherapy of the sternum and later, after confirmation of payment from the health insurance company, she started treatment with tebentafusp. The first three doses were administered during admission to the hospital, with a need to treat cytokine release syndrome by corticosteroids. Later, the administration was performed in an out-patient regimen, without complications, except for a transient elevation of transaminases. The first CT restaging confirmed stable disease; however, the second restaging confirmed a new osteolytic lesion in the processus of Th11. Because of progression, the treatment with tebentafusp was withdrawn after 6 months. Unfortunately, the lesion could not be treated by radiotherapy. Two months later, the patient was urgently admitted to the hospital because of right-sided hemiplegia; MRI revealed bleeding metastatic lesion in the brain stem. In this case report, we present the case of the first patient treated with this drug in the Czech Republic.

Disseminated Cryptococcus neoformans infection involving multiple bones and lung in an immunocompetent patient: a case report

BackgroundCryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent.Case presentationAn Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition.ConclusionsThis case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.

Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

Rare differential diagnosis of an osteolytic lesion of the mandible in a young adult

We report ararely occurring hematologic neoplasm in ayoung adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows acharacteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.

Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2.

Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease caused by mutations in genes responsible for the formation and development of adipocytes. Bone abnormalities are described. However, there is a scarcity of data. To describe bone characteristics in a large CGL1 and 2 case series. Cross-sectional study that assessed bone radiological features of CGL patients of a reference hospital in Fortaleza (CE), Brazil. Patients underwent clinical and bone mineral metabolism evaluation, radiographs of the axial and appendicular skeleton and bone mineral density (BMD) assessment by DEXA (dual energy X-ray absorptiometry). Nineteen patients were included, fourteen were CGL1 and 5, CGL2. Median age was 20 years (8-42) and 58% were women. Median BMI and percentage of body fat were, respectively, 21 Kg/m² (16-24), and 10.5% (7.6-15). The median leptin concentration was 1 ng/mL (0.1-3.3). Diabetes mellitus and dyslipidemia were present in 79% and 63% of patients, respectively. Median calcium and phosphate were normal in almost all patients (95%). Median parathyroid hormone and 25-OH-vitamin D were 23 pg/mL (7-75) and 28 ng/mL (18-43). Osteolytic lesions, osteosclerosis and pseudo-osteopoikylosis, were present in 74%, 42% and 32% of patients, respectively. Lytic lesions were found predominantly in the extremities of long bones, bilaterally and symmetrically, spine was spared. Osteosclerosis was present in axial and appendicular skeleton. Pseudo-osteopoikilosis was found symmetrically in epiphyses of femur and humerus, in addition to the pelvis. BMD Z-score greater than +2.5 SD was observed in 13 patients (68.4%). BMD was higher in CGL1 compared to CGL2 in lumbar spine and total body in adults. No associations were found between high BMD and HOMA-IR (p=0.686), DM (p=0.750), osteosclerosis (p=0.127) or pseudo-osteopoikilosis (p=0.342), and, between pain and bone lesions. Fractures were found in 3 patients. Bone manifestations are prevalent, heterogeneous, and silent in CGL1 and CGL2. Osteolytic lesions are the most common, followed by osteosclerosis and pseudo-osteopoikilosis. Bone mass is high in most cases. There was no pain complaint related to bone lesions. Thus, systematic assessment of bone manifestations in CGL is essential. Studies are needed to better understand its pathogenesis and clinical consequences.

413 Evaluation of Osteoporosis in the Lumbar Spine in Multiple Myeloma Patients Using 18F-NaF PET/CT

INTRODUCTION: Multiple myeloma (MM) is a plasma cell malignancy that structurally damages and weakens the bone, most commonly in the spine, by inducing osteoporosis, osteolytic lesions and pathological fractures. Detecting molecular changes in bone metabolism, such as reduced osteoblastic activity and bone remodeling associated with MM, would allow for early diagnosis of osteoporosis in the lumbar spine and reduce risk for surgical spinal interventions. One such imaging candidate is 18F-NaF PET/CT, a molecular imaging technique sensitive to bone formation. METHODS: The FULIMA clinical trial (NCT02187731) was conducted with 70 newly diagnosed MM patients, with exclusion criteria leaving 33 patients for analysis (9 females, 24 males; mean age 66.6y). Patients’ trabecular body of the L1-L4 vertebrae was analyzed using 18F-NaF PET/CT scans to calculate and evaluate the linear associations among mean standardized NaF uptake value (SUVmean), mean Hounsfield unit (HU) values, and age. Receiver-operating characteristic (ROC) curve analysis with area under the curve (AUC) using the Wilson/Brown method assessed the predictive value of NaF uptake via SUVmean for osteoporosis determined by HU threshold. RESULTS: There was significant positive correlation between HU value and SUVmean (r = 0.64, p < 0.0001) and negative correlations between age and both HU value (r = -0.59, p < 0.0003) and SUVmean (r = -0.53, p = 0.002). Additionally, on average, there was a 29.1% difference in the NaF uptake of MM patients with osteoporosis (SUVmean = 7.0 ± 1.48) compared to normal MM patients (SUVmean = 4.96 ± 1.46). Predictive value of NaF per AUC analysis was 0.857 with p = 0.002. CONCLUSIONS: 18F-NaF PET/CT detects the decreased osteoblastic activity of osteoporosis in the lumbar spine with high precision and accuracy in MM patients, facilitating timely interventions and reducing risk for invasive procedures.

Small cell variant of osteosarcoma of the patella: A rare case report with review of literature

Patella is an uncommon site for the occurrence of bone tumor. Benign tumors are more common as compared to malignant ones. Osteosarcoma of the patella is a very rare tumor with only a few cases reported in the literature. Here, we present a rare case of a small-cell variant of osteosarcoma of the patella. A 12-year-old boy presented to us with pain and swelling over his left knee for 6 months. On X-ray, expansion with osteosclerotic and osteolytic lesions was found in the patella and a suspected diagnosis of osteosarcoma was made. The patient was managed by excisional biopsy of the patella and V–Y plasty of the quadriceps tendon. Results of histopathological and immunohistochemistry analyses were consistent with osteosarcoma of small cell variant. The patient was referred to a higher center after the operation for radiotherapy and chemotherapy. On the final follow-up, after 1 year, the patient was found to have expired. Osteosarcoma of the patella is a rare condition. Further studies with a number of cases and longer duration of follow-up are warranted to obtain better insight that can aid in devising management protocol, prediction of survival, and functional outcome of different surgical interventions for these patients.

An Uncommon Presentation of Chronic Myeloid Leukemia: Osteolytic Bone Lesion as the Initial Manifestation

An Uncommon Presentation of Chronic Myeloid Leukemia: Osteolytic Bone Lesion as the Initial Manifestation

Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2years were treated with Denosumab, 42% with 120mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70mg. To avoid ADRs 500mg of calcium and 400IU of vitamin D orally were used. Initial effective response was reported after 1-3months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120mg, 60 or 70mg in patients < 45 or 50kg for ≥ 12months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

Secondary syphilis: An unusual cause of osteolytic lesion diagnosed by 99mTc-MDP SPECT and presenting features

Herein, we present the case of a 68-year-old woman complaining of pain of the right knee, which was initially misdiagnosed by plain radiography as fracture on inner right tibia plateau but was finally clarified as osteolytic lesion secondary to syphilis affecting the whole right knee. The final diagnosis was made based on the valuable findings from bone scanning, which allows for imaging of abnormalities with much larger extent, a scale that is out of the examination capacity of plain radiography. Bone scanning was employed in this case, coupled with the use of 99mTc-MDP, to assess abnormal bone metabolism at the whole right knee next to the tibia plateau. The imaging results illustrated the diverse features of bone involvement of secondary syphilis, including periostitis, osteolysis as well as osteomyelitis, occurring together or in isolation.

Abstract 5387: Host-derived CCL2 drives prostate cancer bone metastasis via CCND2/STAT3 pathway

Abstract Overexpression of tumor-derived CCL2 has been shown to partially promote prostate cancer (PCa) bone metastasis, but the function of host-derived CCL2 is not fully understood. We first developed a mouse model using intracardiac injection and obtained highly metastatic PCa cell subclones through in vivo selection. The highly metastatic tumor cells were injected intracardially into CCL2 knockout (CCL2 KO) mice and wild-type (WT) controls, and the tumor cell growth and metastasis were monitored weekly by bioluminescence imaging. The osteolytic lesions were evaluated by radiography, micro-computed tomography (microCT) and immunohistochemistry (IHC) staining. The cells in the bone microenvironment were analyzed by flow cytometry. Also, RNA sequencing (RNA-seq) analysis was performed on the cells either from CCL2 KO mice or WT controls. We found that a loss of host-derived CCL2 significantly retarded tumor growth in bone and prolonged mouse survival. In addition, bone density analysis revealed a decrease in osteolytic lesion in CCL2 KO mice, compared to WT controls. Systemically, CCL2 deficiency reduced the proportion of granulocyte-myeloid-derived suppressor cell (G-MDSC) populations with immunosuppressive function and decreased the PCa conditioned medium (CM)-induced osteoclast formation. The enrichment analysis revealed that the dysregulated genes in bone metastatic cells from CCL2 KO mice were significantly enriched in several biological processes, including vitamin metabolism, monoatomic anion homeostasis, immune response, and bone growth. Additionally, we also confirmed that the CCND2/STAT3 pathway is apparently suppressed in the cells from CCL2 KO mice. This study demonstrated that targeting the host-derived CCL2 might be a novel potential anti-metastatic approach. Supported by the NSFC projects (81972766, 81972420, 82173336), as well as grants from the Science and Technology Project of Shenzhen (JCYJ20190809161811237, JCYJ20210324104214040). Key words Host-derived CCL2; Prostate cancer; Bone metastasis; osteoclast; CCND2 Citation Format: Jie Meng, Ming Chang, Siyuan Qin, Xin Huang, Weiping Liang, Haibo Tong, Jian Zhang. Host-derived CCL2 drives prostate cancer bone metastasis via CCND2/STAT3 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5387.